Background: The immune system plays an extensive role in eliminating tumor cells. On the other hand, low-dose irradiation stimulates the immune system.Objective: The present study aimed to investigate the therapeutic outcomes of localized high-dose radiotherapy (LH) alone and combined with total body low-dose irradiation (TB). Material and Methods:In this experimental study, B16F0 tumor cells were injected into the right flank of C57JL/6 mice. The mice were treated with LH alone (13 Gy X-rays to the tumor surface) (LH group) or combined with TB (85 mGy Xrays at the skin) (TB+LH group). Then the tumor volume, the mice's lifespan, the number of lymphocytes extracted from the spleen, and interferon gamma (IFN-γ) production were measured.Results: Reduced number of lymphocytes, compared to non-irradiated mice (control group), was observed in LH and TB+LH groups. However, the identical number of cultured lymphocytes produced a higher level of IFN-γ in irradiated groups. Comparing the irradiated groups, the number of lymphocytes and their IFN-γ production, tumor growth control, and the mice's lifespan were statistically higher in TB+LH group. Conclusion:Observing a higher level of IFN-γ in TB+LH group compared to LH group indicates that low-dose radiation enhanced the stimulating effects of high-dose radiation on the immune system. It caused the mice in TB+LH group to have a more prolonged lifespan and a lower tumor growth rate. Therefore, it is worth our attention for future studies to investigate whether total body low-dose irradiation can be utilized before radiotherapy to enhance its efficiency.